DE69325199T2 - Triazolopyridazine als Antiasthmatika - Google Patents
Triazolopyridazine als AntiasthmatikaInfo
- Publication number
- DE69325199T2 DE69325199T2 DE69325199T DE69325199T DE69325199T2 DE 69325199 T2 DE69325199 T2 DE 69325199T2 DE 69325199 T DE69325199 T DE 69325199T DE 69325199 T DE69325199 T DE 69325199T DE 69325199 T2 DE69325199 T2 DE 69325199T2
- Authority
- DE
- Germany
- Prior art keywords
- group
- compound
- hydroxy
- amino
- substituents selected
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Fee Related
Links
- 239000000924 antiasthmatic agent Substances 0.000 title claims abstract description 18
- 230000001088 anti-asthma Effects 0.000 title claims description 15
- 150000001875 compounds Chemical class 0.000 claims abstract description 192
- 239000000203 mixture Substances 0.000 claims abstract description 92
- 150000003839 salts Chemical class 0.000 claims abstract description 84
- -1 and their production Substances 0.000 claims abstract description 62
- 150000002367 halogens Chemical class 0.000 claims abstract description 39
- 229910052736 halogen Inorganic materials 0.000 claims abstract description 33
- 125000000623 heterocyclic group Chemical group 0.000 claims abstract description 16
- 238000004519 manufacturing process Methods 0.000 claims abstract description 13
- 239000001257 hydrogen Substances 0.000 claims abstract description 6
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 6
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims abstract description 4
- 238000002360 preparation method Methods 0.000 claims description 86
- 238000006243 chemical reaction Methods 0.000 claims description 72
- 125000001424 substituent group Chemical group 0.000 claims description 57
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 43
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 42
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims description 33
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 33
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 claims description 27
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 27
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 26
- 125000006273 (C1-C3) alkyl group Chemical group 0.000 claims description 25
- 206010006482 Bronchospasm Diseases 0.000 claims description 22
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 21
- 230000007885 bronchoconstriction Effects 0.000 claims description 19
- 125000005196 alkyl carbonyloxy group Chemical group 0.000 claims description 16
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 11
- 125000005843 halogen group Chemical group 0.000 claims description 10
- 229910052757 nitrogen Inorganic materials 0.000 claims description 10
- 125000004430 oxygen atom Chemical group O* 0.000 claims description 10
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 9
- 125000002252 acyl group Chemical group 0.000 claims description 9
- 125000003277 amino group Chemical group 0.000 claims description 8
- HGCIXCUEYOPUTN-UHFFFAOYSA-N cyclohexene Chemical compound C1CCC=CC1 HGCIXCUEYOPUTN-UHFFFAOYSA-N 0.000 claims description 8
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 8
- 125000003341 7 membered heterocyclic group Chemical group 0.000 claims description 6
- KAESVJOAVNADME-UHFFFAOYSA-N Pyrrole Chemical compound C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 claims description 6
- 230000003266 anti-allergic effect Effects 0.000 claims description 5
- 229910052760 oxygen Inorganic materials 0.000 claims description 5
- 239000001301 oxygen Substances 0.000 claims description 5
- 229910052717 sulfur Chemical group 0.000 claims description 5
- OQGLMJWGJNCHNA-UHFFFAOYSA-N 2-ethyl-2-[(7-methyl-[1,2,4]triazolo[1,5-b]pyridazin-6-yl)oxymethyl]butane-1-sulfonamide Chemical compound C1=C(C)C(OCC(CC)(CC)CS(N)(=O)=O)=NN2N=CN=C21 OQGLMJWGJNCHNA-UHFFFAOYSA-N 0.000 claims description 4
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 4
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 4
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 3
- ILKSBSWZWUODQX-UHFFFAOYSA-N [1,2,4]triazolo[1,5-b]pyridazine Chemical compound C1=CC=NN2N=CN=C21 ILKSBSWZWUODQX-UHFFFAOYSA-N 0.000 claims description 3
- 150000001925 cycloalkenes Chemical class 0.000 claims description 3
- YKDMDEHXQBJYID-UHFFFAOYSA-N 3-([1,2,4]triazolo[1,5-b]pyridazin-6-yloxy)propane-1-sulfonamide Chemical compound N1=C(OCCCS(=O)(=O)N)C=CC2=NC=NN21 YKDMDEHXQBJYID-UHFFFAOYSA-N 0.000 claims description 2
- AGTZPSPEBPBUFS-UHFFFAOYSA-N 3-ethyl-3-[(7-methyl-[1,2,4]triazolo[1,5-b]pyridazin-6-yl)oxymethyl]pentane-1-sulfonamide Chemical compound C1=C(C)C(OCC(CC)(CCS(N)(=O)=O)CC)=NN2N=CN=C21 AGTZPSPEBPBUFS-UHFFFAOYSA-N 0.000 claims description 2
- GCDVNJPFEJPITA-UHFFFAOYSA-N 4-ethyl-4-[(7-methyl-[1,2,4]triazolo[1,5-b]pyridazin-6-yl)oxymethyl]hexane-1-sulfonamide Chemical compound C1=C(C)C(OCC(CC)(CCCS(N)(=O)=O)CC)=NN2N=CN=C21 GCDVNJPFEJPITA-UHFFFAOYSA-N 0.000 claims description 2
- QRBCZOIEZLETND-UHFFFAOYSA-N 5-ethyl-5-[(7-methyl-[1,2,4]triazolo[1,5-b]pyridazin-6-yl)oxymethyl]heptane-1-sulfonamide Chemical compound C1=C(C)C(OCC(CC)(CCCCS(N)(=O)=O)CC)=NN2N=CN=C21 QRBCZOIEZLETND-UHFFFAOYSA-N 0.000 claims description 2
- 125000000738 acetamido group Chemical group [H]C([H])([H])C(=O)N([H])[*] 0.000 claims description 2
- 125000004434 sulfur atom Chemical group 0.000 claims description 2
- 239000004503 fine granule Substances 0.000 claims 4
- 239000003112 inhibitor Substances 0.000 claims 4
- 230000000694 effects Effects 0.000 abstract description 17
- 125000000217 alkyl group Chemical group 0.000 abstract description 8
- 239000000543 intermediate Substances 0.000 abstract description 2
- 125000003107 substituted aryl group Chemical group 0.000 abstract description 2
- 125000005346 substituted cycloalkyl group Chemical group 0.000 abstract description 2
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 111
- 238000005481 NMR spectroscopy Methods 0.000 description 66
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 52
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 48
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 45
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 45
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 42
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 38
- 238000000921 elemental analysis Methods 0.000 description 38
- 238000002844 melting Methods 0.000 description 37
- 230000008018 melting Effects 0.000 description 37
- 239000002904 solvent Substances 0.000 description 36
- 239000011541 reaction mixture Substances 0.000 description 33
- 239000000243 solution Substances 0.000 description 32
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 31
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 30
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 28
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 26
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 26
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 24
- 238000000034 method Methods 0.000 description 24
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 21
- 239000000741 silica gel Substances 0.000 description 21
- 229910002027 silica gel Inorganic materials 0.000 description 21
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 20
- 238000004440 column chromatography Methods 0.000 description 20
- 238000001816 cooling Methods 0.000 description 20
- 238000010828 elution Methods 0.000 description 19
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 18
- 239000003921 oil Substances 0.000 description 18
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 16
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 16
- XYGZNPKIOSSWBT-UHFFFAOYSA-N 6-chloro-7-methyl-[1,2,4]triazolo[1,5-b]pyridazine Chemical compound N1=C(Cl)C(C)=CC2=NC=NN21 XYGZNPKIOSSWBT-UHFFFAOYSA-N 0.000 description 15
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 15
- 238000009835 boiling Methods 0.000 description 15
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 14
- 235000019341 magnesium sulphate Nutrition 0.000 description 14
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 14
- 239000007858 starting material Substances 0.000 description 13
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 12
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 12
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 12
- 229910052794 bromium Inorganic materials 0.000 description 12
- 239000000460 chlorine Substances 0.000 description 12
- 229910052801 chlorine Inorganic materials 0.000 description 12
- 239000013078 crystal Substances 0.000 description 12
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 11
- OAYLNYINCPYISS-UHFFFAOYSA-N ethyl acetate;hexane Chemical compound CCCCCC.CCOC(C)=O OAYLNYINCPYISS-UHFFFAOYSA-N 0.000 description 11
- 239000012312 sodium hydride Substances 0.000 description 11
- 229910000104 sodium hydride Inorganic materials 0.000 description 11
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 9
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 9
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 9
- 239000007864 aqueous solution Substances 0.000 description 9
- 229910052731 fluorine Inorganic materials 0.000 description 9
- 239000011737 fluorine Substances 0.000 description 9
- 239000005457 ice water Substances 0.000 description 9
- 239000011630 iodine Substances 0.000 description 9
- 229910052740 iodine Inorganic materials 0.000 description 9
- 125000006239 protecting group Chemical group 0.000 description 9
- 239000011780 sodium chloride Substances 0.000 description 9
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 8
- 239000012230 colorless oil Substances 0.000 description 8
- 238000001914 filtration Methods 0.000 description 8
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 8
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 7
- 102100033902 Endothelin-1 Human genes 0.000 description 7
- 101800004490 Endothelin-1 Proteins 0.000 description 7
- GWNVDXQDILPJIG-SHSCPDMUSA-N Leukotriene C4 Natural products CCCCCC=C/CC=C/C=C/C=C/C(SCC(NC(=O)CCC(N)C(=O)O)C(=O)NCC(=O)O)C(O)CCCC(=O)O GWNVDXQDILPJIG-SHSCPDMUSA-N 0.000 description 7
- ZSXGLVDWWRXATF-UHFFFAOYSA-N N,N-dimethylformamide dimethyl acetal Chemical compound COC(OC)N(C)C ZSXGLVDWWRXATF-UHFFFAOYSA-N 0.000 description 7
- GWNVDXQDILPJIG-NXOLIXFESA-N leukotriene C4 Chemical compound CCCCC\C=C/C\C=C/C=C/C=C/[C@H]([C@@H](O)CCCC(O)=O)SC[C@@H](C(=O)NCC(O)=O)NC(=O)CC[C@H](N)C(O)=O GWNVDXQDILPJIG-NXOLIXFESA-N 0.000 description 7
- 239000012280 lithium aluminium hydride Substances 0.000 description 7
- ZNNZYHKDIALBAK-UHFFFAOYSA-M potassium thiocyanate Chemical compound [K+].[S-]C#N ZNNZYHKDIALBAK-UHFFFAOYSA-M 0.000 description 7
- 229940116357 potassium thiocyanate Drugs 0.000 description 7
- 230000008569 process Effects 0.000 description 7
- OISVCGZHLKNMSJ-UHFFFAOYSA-N 2,6-dimethylpyridine Chemical compound CC1=CC=CC(C)=N1 OISVCGZHLKNMSJ-UHFFFAOYSA-N 0.000 description 6
- HVAUUPRFYPCOCA-AREMUKBSSA-N 2-O-acetyl-1-O-hexadecyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCCOC[C@@H](OC(C)=O)COP([O-])(=O)OCC[N+](C)(C)C HVAUUPRFYPCOCA-AREMUKBSSA-N 0.000 description 6
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- 241000700198 Cavia Species 0.000 description 6
- 241000700199 Cavia porcellus Species 0.000 description 6
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 6
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- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 6
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- 229920006395 saturated elastomer Polymers 0.000 description 6
- FVAUCKIRQBBSSJ-UHFFFAOYSA-M sodium iodide Chemical compound [Na+].[I-] FVAUCKIRQBBSSJ-UHFFFAOYSA-M 0.000 description 6
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- 125000004432 carbon atom Chemical group C* 0.000 description 5
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- 125000004916 (C1-C6) alkylcarbonyl group Chemical group 0.000 description 4
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- 125000004672 ethylcarbonyl group Chemical group [H]C([H])([H])C([H])([H])C(*)=O 0.000 description 4
- 239000000706 filtrate Substances 0.000 description 4
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- 125000002485 formyl group Chemical group [H]C(*)=O 0.000 description 4
- 239000008273 gelatin Substances 0.000 description 4
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- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 4
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- 238000007873 sieving Methods 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- RAOIDOHSFRTOEL-UHFFFAOYSA-N tetrahydrothiophene Chemical compound C1CCSC1 RAOIDOHSFRTOEL-UHFFFAOYSA-N 0.000 description 1
- 239000004408 titanium dioxide Substances 0.000 description 1
- 238000009281 ultraviolet germicidal irradiation Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
- C07D487/04—Ortho-condensed systems
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
- A61P11/06—Antiasthmatics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/08—Antiallergic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
- A61P7/02—Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Public Health (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pulmonology (AREA)
- Engineering & Computer Science (AREA)
- Pain & Pain Management (AREA)
- Diabetes (AREA)
- Hematology (AREA)
- Immunology (AREA)
- Rheumatology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Agricultural Chemicals And Associated Chemicals (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Macromolecular Compounds Obtained By Forming Nitrogen-Containing Linkages In General (AREA)
- Plural Heterocyclic Compounds (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP6178092 | 1992-03-18 | ||
| JP21890492 | 1992-08-18 | ||
| JP1456093 | 1993-02-01 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| DE69325199D1 DE69325199D1 (de) | 1999-07-15 |
| DE69325199T2 true DE69325199T2 (de) | 1999-12-16 |
Family
ID=27280691
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DE69325199T Expired - Fee Related DE69325199T2 (de) | 1992-03-18 | 1993-03-17 | Triazolopyridazine als Antiasthmatika |
Country Status (22)
| Country | Link |
|---|---|
| US (1) | US5389633A (es) |
| EP (1) | EP0562439B1 (es) |
| CN (1) | CN1040874C (es) |
| AT (1) | ATE181075T1 (es) |
| AU (1) | AU654430B2 (es) |
| CA (1) | CA2091874A1 (es) |
| DE (1) | DE69325199T2 (es) |
| DK (1) | DK0562439T3 (es) |
| EE (1) | EE9400357A (es) |
| ES (1) | ES2132147T3 (es) |
| FI (1) | FI104076B1 (es) |
| GR (1) | GR3030817T3 (es) |
| HK (1) | HK1009700A1 (es) |
| HU (2) | HU218791B (es) |
| LT (1) | LT3200B (es) |
| LV (1) | LV10456B (es) |
| MY (1) | MY108967A (es) |
| NO (1) | NO300774B1 (es) |
| NZ (1) | NZ247171A (es) |
| PH (1) | PH29998A (es) |
| RU (1) | RU2130458C1 (es) |
| TW (1) | TW255891B (es) |
Families Citing this family (29)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5962490A (en) * | 1987-09-25 | 1999-10-05 | Texas Biotechnology Corporation | Thienyl-, furyl- and pyrrolyl-sulfonamides and derivatives thereof that modulate the activity of endothelin |
| US5464853A (en) * | 1993-05-20 | 1995-11-07 | Immunopharmaceutics, Inc. | N-(5-isoxazolyl)biphenylsulfonamides, N-(3-isoxazolyl)biphenylsulfonamides and derivatives thereof that modulate the activity of endothelin |
| US5514691A (en) * | 1993-05-20 | 1996-05-07 | Immunopharmaceutics, Inc. | N-(4-halo-isoxazolyl)-sulfonamides and derivatives thereof that modulate the activity of endothelin |
| US5571821A (en) * | 1993-05-20 | 1996-11-05 | Texas Biotechnology Corporation | Sulfonamides and derivatives thereof that modulate the activity of endothelin |
| US5594021A (en) * | 1993-05-20 | 1997-01-14 | Texas Biotechnology Corporation | Thienyl-, furyl- and pyrrolyl sulfonamides and derivatives thereof that modulate the activity of endothelin |
| US5591761A (en) * | 1993-05-20 | 1997-01-07 | Texas Biotechnology Corporation | Thiophenyl-, furyl-and pyrrolyl-sulfonamides and derivatives thereof that modulate the activity of endothelin |
| US5736509A (en) * | 1990-12-14 | 1998-04-07 | Texas Biotechnology Corporation | Cyclic peptide surface feature mimics of endothelin |
| US5482939A (en) * | 1992-03-18 | 1996-01-09 | Takeda Chemical Industries, Ltd. | Triazolopyridazine compounds, their production and use |
| CA2120997A1 (en) * | 1993-04-12 | 1994-10-13 | Akio Miyake | Triazolopyridazine derivatives, their production and use |
| US6030991A (en) * | 1993-05-20 | 2000-02-29 | Texas Biotechnology Corp. | Benzenesulfonamides and the use thereof to modulate the activity of endothelin |
| US6613804B2 (en) | 1993-05-20 | 2003-09-02 | Encysive Pharmaceuticals, Inc. | Biphenylsulfonamides and derivatives thereof that modulate the activity of endothelin |
| US6342610B2 (en) | 1993-05-20 | 2002-01-29 | Texas Biotechnology Corp. | N-aryl thienyl-, furyl-, and pyrrolyl-sulfonamides and derivatives thereof that modulate the activity of endothelin |
| TW304878B (es) * | 1993-09-21 | 1997-05-11 | Takeda Pharm Industry Co Ltd | |
| AU695377B2 (en) * | 1994-09-16 | 1998-08-13 | Takeda Chemical Industries Ltd. | Triazolopyridazines process and intermediates for their preparation and their use as medicaments |
| US5977117A (en) | 1996-01-05 | 1999-11-02 | Texas Biotechnology Corporation | Substituted phenyl compounds and derivatives thereof that modulate the activity of endothelin |
| US5958905A (en) * | 1996-03-26 | 1999-09-28 | Texas Biotechnology Corporation | Phosphoramidates, phosphinic amides and related compounds and the use thereof to modulate the activity of endothelin |
| US5804585A (en) | 1996-04-15 | 1998-09-08 | Texas Biotechnology Corporation | Thieno-pyridine sulfonamides derivatives thereof and related compounds that modulate the activity of endothelin |
| AU7079998A (en) | 1997-04-25 | 1998-11-24 | Takeda Chemical Industries Ltd. | Condensed pyridazine derivatives, their production and use |
| JP3455233B2 (ja) | 1997-04-28 | 2003-10-14 | テキサス・バイオテクノロジー・コーポレイシヨン | エンドテリン介在障害治療用のスルホンアミド類 |
| US5783705A (en) * | 1997-04-28 | 1998-07-21 | Texas Biotechnology Corporation | Process of preparing alkali metal salys of hydrophobic sulfonamides |
| CA2319426A1 (en) * | 1998-03-04 | 1999-09-10 | Kenichirou Kiyoshima | Triazolo-pyridazine derivatives for the treatment of chronic obstructive pulmonary diseases |
| AU6003099A (en) | 1998-10-06 | 2000-04-26 | Takeda Chemical Industries Ltd. | Fused pyridazine compounds, process for the preparation of the same and uses thereof |
| CA2348022A1 (en) | 1998-10-21 | 2000-04-27 | Takeda Chemical Industries, Ltd. | Condensed pyridazine derivatives, their production and use |
| EP2240486B1 (de) * | 2008-02-05 | 2015-09-09 | Sanofi | Triazoliumsalze als par1-inhibitoren, ihre herstellung und verwendung als arzneimittel |
| CN102791715B (zh) | 2009-12-31 | 2016-04-27 | 卡洛斯三世国家癌症研究中心基金会 | 用作激酶抑制剂的三环化合物 |
| WO2012098387A1 (en) | 2011-01-18 | 2012-07-26 | Centro Nacional De Investigaciones Oncológicas (Cnio) | 6, 7-ring-fused triazolo [4, 3 - b] pyridazine derivatives as pim inhibitors |
| WO2013005041A1 (en) | 2011-07-07 | 2013-01-10 | Centro Nacional De Investigaciones Oncológicas (Cnio) | Tricyclic heterocyclic compounds as kinase inhibitors |
| WO2013004984A1 (en) | 2011-07-07 | 2013-01-10 | Centro Nacional De Investigaciones Oncologicas (Cnio) | Tricyclic compounds for use as kinase inhibitors |
| WO2013005057A1 (en) | 2011-07-07 | 2013-01-10 | Centro Nacional De Investigaciones Oncológicas (Cnio) | New compounds |
Family Cites Families (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3915968A (en) | 1973-09-21 | 1975-10-28 | Lepetit Spa | Triazolopyridazines |
| US4136182A (en) | 1976-05-26 | 1979-01-23 | The Dow Chemical Company | Triazolopyridazines used to alleviate bronchial spasms |
| PH27291A (en) * | 1989-01-31 | 1993-05-04 | Takeda Chemical Industries Ltd | Imidazolpyrimidazines their production and use |
| EP0440119A1 (en) * | 1990-01-31 | 1991-08-07 | Takeda Chemical Industries, Ltd. | Imidazopyridazine compounds, their production and use |
| DE69106902T2 (de) * | 1990-03-01 | 1995-07-06 | Takeda Chemical Industries Ltd | Imidazopyridazine, ihre Herstellung und Verwendung. |
-
1993
- 1993-03-05 LT LTIP390A patent/LT3200B/lt not_active IP Right Cessation
- 1993-03-06 TW TW082101665A patent/TW255891B/zh active
- 1993-03-10 MY MYPI93000429A patent/MY108967A/en unknown
- 1993-03-12 RU RU93004584A patent/RU2130458C1/ru active
- 1993-03-16 NZ NZ247171A patent/NZ247171A/en unknown
- 1993-03-16 AU AU35269/93A patent/AU654430B2/en not_active Ceased
- 1993-03-17 ES ES93104367T patent/ES2132147T3/es not_active Expired - Lifetime
- 1993-03-17 LV LVP-93-189A patent/LV10456B/en unknown
- 1993-03-17 EP EP93104367A patent/EP0562439B1/en not_active Expired - Lifetime
- 1993-03-17 CA CA002091874A patent/CA2091874A1/en not_active Abandoned
- 1993-03-17 FI FI931190A patent/FI104076B1/fi active
- 1993-03-17 AT AT93104367T patent/ATE181075T1/de not_active IP Right Cessation
- 1993-03-17 DE DE69325199T patent/DE69325199T2/de not_active Expired - Fee Related
- 1993-03-17 DK DK93104367T patent/DK0562439T3/da active
- 1993-03-17 NO NO930974A patent/NO300774B1/no not_active IP Right Cessation
- 1993-03-17 PH PH45897A patent/PH29998A/en unknown
- 1993-03-17 US US08/032,296 patent/US5389633A/en not_active Expired - Fee Related
- 1993-03-17 HU HU9300759A patent/HU218791B/hu not_active IP Right Cessation
- 1993-03-18 CN CN93103370A patent/CN1040874C/zh not_active Expired - Fee Related
-
1994
- 1994-11-10 EE EE9400357A patent/EE9400357A/xx unknown
-
1995
- 1995-05-31 HU HU95P/P00146P patent/HU211326A9/hu unknown
-
1998
- 1998-09-08 HK HK98110535A patent/HK1009700A1/xx not_active IP Right Cessation
-
1999
- 1999-07-20 GR GR990401905T patent/GR3030817T3/el unknown
Also Published As
| Publication number | Publication date |
|---|---|
| FI104076B (fi) | 1999-11-15 |
| DK0562439T3 (da) | 1999-11-15 |
| HU218791B (hu) | 2000-12-28 |
| NO930974L (no) | 1993-09-20 |
| FI931190A (fi) | 1993-09-19 |
| ES2132147T3 (es) | 1999-08-16 |
| EP0562439A1 (en) | 1993-09-29 |
| LTIP390A (lt) | 1994-08-25 |
| HK1009700A1 (en) | 1999-06-04 |
| DE69325199D1 (de) | 1999-07-15 |
| LV10456B (en) | 1995-10-20 |
| EP0562439B1 (en) | 1999-06-09 |
| RU2130458C1 (ru) | 1999-05-20 |
| LV10456A (lv) | 1995-02-20 |
| LT3200B (en) | 1995-03-27 |
| HU211326A9 (en) | 1995-11-28 |
| TW255891B (es) | 1995-09-01 |
| CN1077958A (zh) | 1993-11-03 |
| FI931190A0 (fi) | 1993-03-17 |
| AU3526993A (en) | 1993-09-23 |
| CA2091874A1 (en) | 1993-09-19 |
| PH29998A (en) | 1996-10-29 |
| GR3030817T3 (en) | 1999-11-30 |
| EE9400357A (et) | 1996-04-15 |
| HUT65935A (en) | 1994-08-29 |
| NO930974D0 (no) | 1993-03-17 |
| AU654430B2 (en) | 1994-11-03 |
| US5389633A (en) | 1995-02-14 |
| NO300774B1 (no) | 1997-07-21 |
| NZ247171A (en) | 1994-09-27 |
| HU9300759D0 (en) | 1993-06-28 |
| CN1040874C (zh) | 1998-11-25 |
| ATE181075T1 (de) | 1999-06-15 |
| MY108967A (en) | 1996-11-30 |
| FI104076B1 (fi) | 1999-11-15 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| 8364 | No opposition during term of opposition | ||
| 8339 | Ceased/non-payment of the annual fee |